运动代谢物如何影响重症肌无力？2025双向MR研究揭示因果机制

Exercise-related metabolites are a class of bioactive substances produced or regulated during physical activity, encompassing various types of substances such as amino acids (e.g., glutamine, branched-chain amino acids, citrulline), metabolic products (e.g., lactate, ketone bodies), and hormones (e.g., testosterone, growth hormone). These metabolites play indispensable roles in energy metabolism, protein synthesis, tissue repair, and immune regulation, serving as a crucial foundation for maintaining skeletal muscle function and metabolic homeostasis (DOI: 10.3390/foods13091424). Among them, glutamine, citrulline, branched-chain amino acids, iron supplements, and vitamins can be ingested as oral supplements, effectively enhancing their circulating levels through exogenous supplementation. In recent years, studies have found that uric acid, an endogenous metabolite, is negatively associated with myasthenia gravis (MG), suggesting that higher levels of uric acid may have a protective effect on MG (DOI: 10.1111/cns.70361). Another study confirmed that higher iron levels also have a protective effect on MG (DOI: 10.1002/brb3.70848). Additionally, large-scale Mendelian randomization (MR) studies combined with observational analyses have shown that time spent watching television, body mass index (BMI), and waist circumference are positively correlated with the risk of MG. Sedentary behavior partially mediates the effect of BMI on MG, indicating that lack of exercise may increase MG risk by promoting obesity. Moreover, sedentary behavior also increases the risk of late-onset myasthenia gravis (LOMG) (DOI: 10.1016/j.bbih.2025.100975, DOI: 10.1186/s12883-023-03343-y). These studies not only suggest a causal relationship between certain endogenous metabolites and the onset of MG but also indicate that physical exercise, such as reducing sedentary behavior and controlling weight, may have a protective effect on MG. Currently, the causal relationships between common exercise-related metabolites, such as glutamine, citrulline, testosterone, and lactate, and the risks of MG and LOMG remain unclear. Based on this, this study employs a two-sample bidirectional Mendelian randomization method to systematically evaluate the causal relationship between exercise-related metabolites and the risk of myasthenia gravis.